The present invention relates to a method and apparatus for non-invasively determining light-sleep and deep-sleep stages by sensing peripheral pulse signals related to the systemic circulation of the subject. The invention is particularly useful when utilizing a peripheral arterial tone (PAT) sensor, such as disclosed in U.S. patent application Ser. No. 10/195,464, filed Jul. 16, 2002, U.S. patent application Ser. No. 10/471,580, filed Sep. 12, 2003, and U.S. patent application Ser. No. 10/520,273, filed Jan. 18, 2005, all assigned to the same assignee as the present application, the descriptions of which are incorporated herein by reference, and the invention is therefore described below with respect to such sensors.
To facilitate understanding the following description, there are set forth below the meanings of a number of acronyms frequently used therein.
REM rapid eye movement (sleep stage)
NREM non-rapid eye movement (sleep stage)
PAT peripheral arterial tone (signal)
AMP PAT signal amplitude
EEG electroencephalogram—electrical currents associated with the brain
EMG electromyogram—electrical currents associated with muscles
EOG electrooculography—measuring the resting potential of the retina
ANS automatic nervous system
OSA obstructive sleep apnea
OSAS obstructive sleep apnea syndrome
RDI respiratory disturbance index
PSG Polysomnography
IPP inter-pulse period (heart-rate)
DFA detrended fluctuation analysis
VLF peak of the very low frequency spectral density
LF peak of the low frequency spectral density
ULF peak of the ultra-low frequency spectral density
HF peak of the high frequency spectral density
Spec Ratio of LF to HF
NF neighboring filter
ROC Receiver Operating Characteristic (curve)
AASM American Academy of Sleep Medicine
Detecting various sleep-state conditions, particularly sleep-wake status and REM sleep stages versus NREM sleep stages, is commonly used in the determination of various medical conditions, particularly obstructive sleep conditions such as OSA, and REM related apnea. At the present time, detecting the various sleep-state conditions is commonly done by PSG in a sleep laboratory equipped with specialized instruments for sensing various conditions, particularly the EEG signal, and utilizing the results of the sensed conditions for determining the sleep state. The above-cited U.S. patent application Ser. No. 10/195,464 filed Jul. 16, 2002 utilizes an external probe applied to peripheral body location, such as a digit (finger or toe) of the individual, for detecting peripheral pulse signals related to the systemic circulation of the subject. The preferred embodiment therein disclosed utilizes a PAT probe for detecting changes in the peripheral vascular bed volume of the subject. Likewise, the above-cited U.S. patent application Ser. No. 10/520,273, filed Jan. 18, 2005, utilizes an external probe capable of being applied at virtually any body site of the individual, for detecting peripheral pulse signals related to the systemic circulation of the subject.
The present invention is directed particularly to detecting and distinguishing epochs of deep-sleep from epochs of light-sleep using a probe applied to the individual for sensing peripheral pulse signals related to the systemic circulation of the subject, which can be used for unattended ambulatory sleep monitoring, not requiring the sensors (e.g., EEG sensors) or other specialized instruments provided in a sleep laboratory.
The invention is particularly effective when using a PAT probe described in the above-cited U.S. application Ser. Nos. 10/195,464, 10/471,580, and 10/520,273, for detecting changes in the peripheral vascular bed volume of the individual, and is therefore described below particularly with respect to the use of such sensors. For the sake of brevity, the construction and operation of such PAT sensors are not described herein, but are available in the above-cited U.S. application Ser. Nos. 10/195,464, 10/471,580, and 10/520,273, incorporated herein by reference for this purpose. While the invention preferably uses such a PAT sensor, it will be appreciated that the invention could use other sensors for sensing peripheral pulse signals. A number of such other sensors are well known to the art. These include, but are not restricted to; skin optical density or skin surface-reflectivity devices, optical plethysmographs, (also known as photo-plethysmograps), Doppler ultrasound devices, laser Doppler device, pulse oximeters, segmental plethysmographs, circumferential strain gauge devices, isotope washout techniques, thermal washout techniques, electromagnetic techniques, Hall effect sensors, and the like for sensing peripheral pulse signal related to the systemic circulation of the subject.
Non-Rapid Eye Movement (NREM) sleep was traditionally classified into four stages, where stage 1 was defined as drowsiness (just falling asleep); stage 2 as light-sleep, and stages 3 and 4 as deep sleep, which is considered the more refreshing sleep. Both Stages 1 and 2 NREM sleep, classified as light-sleep, are characterized by theta EEG activity. In stage 1 NREM sleep, there may be slow vertical eye rolling while stage 2 of NREM sleep is characterized by sleep spindles and/or K complexes, no eye movements and reduced EMG activity. Stages 3 and 4 NREM sleep, classified as deep sleep, are characterized by delta EEG activity (which is the reason for the common term describing these stages as slow-wave sleep), no eye movements (although the EOG channels commonly show EEG artifacts), and even further diminished EMG activity (Lavie et al., 2002; Rechtschaffen and Kales, 1968). Given the more restorative nature of deep sleep, and the common findings of increased deep sleep following sleep deprivation or treatment for sleep disorders, it is of substantial clinical importance to distinguish between light-sleep and deep-sleep stages.
Recently, the AASM Visual Scoring Task Force re-examined these rules and came up with a new terminology for sleep stages. Since no evidence was found to justify dividing slow wave sleep into two stages, i.e. stages 3 and 4 of NREM sleep, it was proposed to combine these into a single stage of deep sleep (Silber et al., 2007) However, despite coming up with new scoring criteria, as with its predecessor (Rechtschaffen & Kales, 1968) the activity of the autonomic nervous system (ANS) still does not play a major role in scoring sleep stages, despite increasing evidence for substantial and differential activities of this system in the various sleep stages. In other words, regardless of the EEG changes measured via surface electrodes, light and deep sleep seem to differ by autonomic activations manifested predominantly as higher and more stable parasympathetic activity in deep sleep than light NREM sleep (Dvir et al., 2002; Herscovici et al., 2007; Lavie et al., 2000; Narkiewicz et al., 1998; Penzel et al., 2000; Penzel et al., 2003; Penzel et al., 2004; Pressman and Fry, 1989; Villa et al., 2000; Virtanen et al., 2007). Thus, ANS such as heart rate, heart rate variability or peripheral arterial tone may be of significant importance in evaluating the quality of NREM sleep.
The Watch-PAT 100 (WP100 or WP200 further version of the same system) is an ambulatory sleep recorder, which is based predominantly on recordings of the peripheral arterial tone (PAT) signal and pulse rate (two important outputs of the autonomic nervous system), actigraphy and pulse oximetry (Bar et al, 2004, Penzel et al, 2004, Pillar et al 2003). It has been shown to accurately detect sleep vs. wakefulness (Hedner et al., 2004), as well as to detect REM sleep (Dvir et al., 2002; Herscovici et al., 2007; Lavie et al., 2000). Given the well established changes of the autonomic nervous system characteristics in patients with obstructive sleep apnea (Aydin et al., 2004; Brooks et al., 1999; Jo et al., 2005; Narkiewicz et al., 1998; Narkiewicz and Somers, 1997; Penzel et al., 2000; Penzel et al., 2003; Pepin et al., 1994), the WP100 has been tested on both normal subjects and patients with OSA (Bar et al., 2003; Dvir et al., 2002; Hedner et al., 2004; Herscovici et al., 2007; Lavie et al., 2000; Penzel et al., 2004; Pillar et al., 2003). However, the ability to distinguish between light-sleep and deep sleep based on autonomic nervous system (ANS) outputs monitored by the WP100 has not been examined.
Deep sleep has been shown to be associated with increased parasympathetic activity (projected in heart rate and heart rate variability), and more regular and stable heart rate (Berlad et al., 1993; Bonnet and Arand, 1997; Brandenberger et al., 2005; Burgess et al., 1999; Busek et al., 2005; Elsenbruch et al., 1999; Ferri et al., 2000; Kirby and Verrier, 1989; Kodama et al., 1998; Liguori et al., 2000; Monti et al., 2002; Negoescu and Csiki, 1989; Noll et al., 1994; Okada et al., 1991; Penzel et al., 2003; Pressman and Fry, 1989; Somers et al., 1993; Takeuchi et al., 1994; Trinder et al., 2001; Villa et al., 2000). Therefore it would be highly desirable to develop an algorithm which will allow detecting and distinguishing light from deep sleep solely based on a sensor for sensing a peripheral pulse signal related to the systemic circulation of a subject. A PAT probe is particularly useful for the this purpose since the vascular tone and the pulse rate both are channels of the PAT probe in the WP100. This would allow for testing the hypothesis that autonomic nervous system output changes are sleep-stage dependent. As mentioned, other sensors for sensing peripheral pulse signals could be used to this end.